• Title/Summary/Keyword: Acute toxicity

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Structures and some Properties of the Antimicrobial Compounds in the Red Alga, Symphyocladia latiuscula (참보라색우무에서 추출한 항균물질의 구조 및 특성)

  • LIM Chi-Won;LEE Jong-Soo;CHO Young-Je
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.33 no.4
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    • pp.280-287
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    • 2000
  • Three antimicrobial compounds (SL-l, SL-2 and SL-3) were isolated and identified from the marine red alga, Symphyocladia latiuscula. In addition, their biological functionalities such as cytotoxicity and desmutagenic activity were investigated. From the cryophyllized S. JatiuscuJa, SL-l, SL-2 and SL-3 were purified by solvent extractions and HPLC.SL-2 was crystallized in benzene-diethyl ether solvent. On the EI-MS spectra, it was found that they had three bromines in their structure which showed typical signal strength ratios at $M^+, [M+2]^+, [M+4]^+, [M+6]^+ (13: 38: 37: 12)$. $SL-l$ was identified as 2,3,6-tribromo-4,5-dihydroxybenzyl alcohol ($C_8H_7Br_3O_3, MW=374$) by NMR and MS spectra. SL-2 was assigned as 2,3,6-tribromo-4,5-dihydroxybenzyl methyl ether ($C_8H_7Br_3O_3, MW=388$) and confirmed by X-ray crystallographic analysis. SL-3 was presumed as an isomer of SL-2. Methanol extract of the S. latiuscula showed antimicrobial activities against all strains tested (bacteria, 15 strains; yeasts, 17 strains; fungi, 4 strains), much or less. The strongest inhibition activity of the methanol extract was to the Vibrio mimicus ($50 {\mu}g/ml$) and V. vulnificus ($50 {\mu}g/ml$). The mice injected intraperitoneally with 3 mg of SL-l and 5 mg of 5L-2 showed no acute toxicity response. SL-2 showed higher desmutagenic activity than SL-l against PhIP and MeIQx.

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The Clinical Characteristics and Mortality Factors of Patients with Hemorrhagic Complications after Anticoagulation Therapy with Warfarin (와파린 항응고 유지요법 중 발생한 급성출혈의 임상소견과 사망관련 인자)

  • Lee, Se-Ho;Kim, Nam-Kyu;Sohn, Chang-Hwan;Kim, Jung-Hun;Kim, Won;Lim, Kyung-Soo;Oh, Bum-Jin
    • Journal of The Korean Society of Clinical Toxicology
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    • v.7 no.2
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    • pp.164-171
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    • 2009
  • Purpose: The number of patients who take warfarin is growing and so is the number of complications. Hemorrhage is the major complication, but the clinical characteristics and outcomes have not been determined for Korean patients. Therefore, we tried to evaluate the characteristics of the patients with hemorrhagic complications after taking warfarin as anticoagulation therapy. Methods: We retrospectively reviewed the medical records of the patients who visited the emergency room with bleeding complications after taking warfarin anticoagulation at the out-patient clinic for 1 year from 1 st January 2008. We compared between two groups (the major hemorrhage group vs. the minor hemorrhage group) according to the clinical criteria, the unstable vital signs that required blood transfusion, transfusion more than 2 units of blood, the need for further laboratory follow-up, the need for interventional treatment and the development of critical complications or death due to bleeding. Results: There were 150 patients who met the criteria and had acute hemorrhagic complications (the major group: 90 patients and the minor group: 60 patients). In the major hemorrhage group, the frequent sites of bleeding were the gastro-intestinal system (40 patients), lung (14 patients) and intracranium (7 patients). At the emergency room, the major group showed a higher initial INR of the activated prothrombin time than did the minor group (p=0.02). The bleeding sites of the fatal cases were the gastro-intestinal system (3 patients), lung (3 patients) and intracranium (3 patients), but the percentage of fatality was the highest for intracranium bleeding. Conclusion: In the major hemorrhage group, gastrointestinal bleeding was the most frequent complication and fatality was the highest for intracranium bleeding. An initially higher INR showed a greater risk of major bleeding, but not more fatalities.

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Examinations on sedation, anaesthetic and toxic effect of Isoeugenol for olive-flounder (Paralichthys olivaceus) (Isoeugenol의 넙치(Paralichthys olivaceus)에 대한 진정, 마취 및 독성효과 검토)

  • Shin, Gee-wook;Shin, Yong-seung;Kim, Young-rim;Lee, Eun-young;Yang, Hyang-hee;Palaksha, K.J.;Huh, Nam-eung;Yeon, Seong-chan;Lee, Hee-chun;Oh, Myung-ju;Joh, Seong-joon;Kang, Seung-won;Jung, Tae-sung
    • Korean Journal of Veterinary Research
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    • v.45 no.2
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    • pp.303-309
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    • 2005
  • Olive flounder (Paralichthys olivaceus) is the major mariculture fish in Korea. The annual aquaculture production of olive flounder in Korea during the period of 2003 was 300,000 ton (2002 Statistics, Ministry of Maritime Affairs & Fisheries, Korea Government). Anesthetics is very necessary in aquaculture to minimize stress and damage during harvesting, grading, transportation, spawning induction and handling to fish. In the present study, isoeugenol as new anesthetic in marine fish, especially olive flounder, was examined to know the efficacy and proper concentration. As a result, olive flounder adult was exhibited sedation at 5 ppm at 10 and $15^{\circ}C$, and 7.5 ppm at $20^{\circ}C$, respectively. Anesthesia was required at least 10, 7.5 and 10 ppm at $10^{\circ}C$, $15^{\circ}C$ and at $20^{\circ}C$, respectively. In case of fry, the effect of sedation was observed from 2.5 ppm at $10^{\circ}C$ and 5 ppm at 15 and $20^{\circ}C$, respectively. Anesthesia was observed from 2.5 ppm at $10^{\circ}C$, 5 ppm at 15 and $20^{\circ}C$, respectively. In acute toxicity test, it was impossible to explore $LD_{50}$ with the concentration of isoeugenol adult at $15^{\circ}C$ used, but over immersion volume of 15 ppm at $15^{\circ}C$ was observed mortality in fry. Based on the present study, isoeugenol was identified as a safe and active anesthetic to olive flounder.

Differential Diagnosis of Chemical-induced Hepatobiliary Toxicities Using a New Hepatobiliary Imaging Agent in Mice

  • Ryu, Chong-Kun;Pie, Jae-Eun;Choe, Jae-Gol;Cheon, Joon;Sohn, Jeong-Won;Jurgen Seidel;David S. Paik;Michael V. Green;Chang H. Paik;Kim, Meyoung-Kon
    • Environmental Mutagens and Carcinogens
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    • v.21 no.1
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    • pp.1-8
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    • 2001
  • We have synthesized $^{99m}$Tc-mercaptoacetyltriglycine (MAG3)-biocytin as a new imaging agent for hepatobiliary scintigraphy. The aim of this study was to evaluate the usefulness of $^{99m}$Tc-MAG3-biocytin scintigraphy in differentiating carbon tetrachloride ( $CCl_4$)-induced hepatotoxicity from $\alpha$-naphthylisothiocyanate (ANIT)-induced cholestasis in mice, which reflecting the differential diagnosis of neonatal jaundice caused by neonatal hepatitis from congenital biliary atresia in humans. Methods: Balb/c mice (female, 20 g, n=4-6) were pretreated with $CCl_4$(0.5 or $1.0m\ell$/kg) and ANIT ($150 or 300 m\ell$/kg) 18 h before scintigraphy. Biochemical and histopathological examinations showed a pattern of typical acute hepatitis (increase of transaminases and hepatocellular necnsis) in $CCl_4$-treated mice and cholestasis (increase of alkaline phosphatase and ${\gamma}$-glutamyltransferase, and biliary hyperplasia) in ANIT-treated mice, respectively, Mice were fasted at least 4 hr prior to the intravenous injection of $^{99m}$Tc-MAG3-biocytin (18.5 MBq/20$\mu\textrm{g}$) in 2% human serum albumin in saline. Scintigraphy was performed with a ${\gamma}$-camera equipped with a 1-mm diameter pin-hole collimator for 30 min and images were acquired every 15 s. We compared the values of physical parameters, such as peak liver/heart ratio ($${\gamma}$_{max}$) and peak ratio time ($t_{max}$) far $^{99m}$Tc-MAG3-biocytin scintigraphy. Results: Scintigraphic parameters of the $CCl_4$-pretreated (0.5 $m\ell$/kg) group showed a 81.9% decrease of r$_{max}$, and 42.2% decrease of $t_{max}$, whereas the ANIT-pretreated ( $150m\ell$/kg) group showed a 53% decrease of $r_{max}$, and 2.36-fold increase of $t_{max}$, (P<0.05). These results demonstrate that the decrease of $r_{max}$ and the shortening of $t_{max}$ are characteristic features for hepatotoxicity, in contrast to the increase of $t_{max}$ and decrease of $r_{max}$ for biliary hyperplasia. Conclusion: $^{99m}$Tc-MAG3-biocytin hepatobiliary scintigraphy can distinguish hepatitis from cholestasis in mice model and may be similarly useful in humans which differentiating the cause of neonatal jaundice in clinical study.cal study.cal study.cal study.

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Toxicological effects of pesticides on loach in rice paddy (벼 재배 논 서식 미꾸리에 대한 농약의 영향)

  • Park, Yeon-Ki;Park, Kyeong-Hoon;Joo, Jin-Bok;Kyung, Kee-Sung;Kim, Byung-Seok;Shin, Jin-Sup;Ryu, Gap-Hee;Bae, Chul-Han;Lee, Kyu-Seung
    • The Korean Journal of Pesticide Science
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    • v.7 no.2
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    • pp.131-138
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    • 2003
  • A toxicological study of the pesticides for rice paddy to loach was conducted with iprobenfos 17% GR, diazinon 3 % GR, and butachlor 5 % GR to establish the field test method and their toxicological effects on loach under the actual field conditions. The type C of cage was more effective in the sense of a little stress from the cage. The nets for shading and for preventing the birds were necessary to maintain the water temperature and to prevent the predators. The cumulative mortality of loach exposed to iprobenfos 17% GR, diazinon 3% GR and butachlor 5% GR were 10, 55 and 22%, respectively, during 7 days of exposure. The averaged concentration of the pesticides in paddy water 2 days after application were 1.67, 0.22 and 0.26 mg/L, and mortalities were 7, 50 and 17%, respectively, representing the similar results with acute toxicity $(48h-LC_{50})$.

In vivo Pharmacokinetics, Activation of MAPK Signaling and Induction of Phase II/III Drug Metabolizing Enzymes/Transporters by Cancer Chemopreventive Compound BHA in the Mice

  • Hu, Rong;Shen, Guoxiang;Yerramilli, Usha Rao;Lin, Wen;Xu, Changjiang;Nair, Sujit;Kong, Ah-Ng Tony
    • Archives of Pharmacal Research
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    • v.29 no.10
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    • pp.911-920
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    • 2006
  • Phenolic antioxidant butylated hydroxyanisole (BHA) is a commonly used food preservative with broad biological activities, including protection against chemical-induced carcinogenesis, acute toxicity of chemicals, modulation of macromolecule synthesis and immune response, induction of phase II detoxifying enzymes, as well as its undesirable potential tumor-promoting activities. Understanding the molecular basis underlying these diverse biological actions of BHA is thus of great importance. Here we studied the pharmacokinetics, activation of signaling kinases and induction of phase II/III drug metabolizing enzymes/transporter gene expression by BHA in the mice. The peak plasma concentration of BHA achieved in our current study after oral administration of 200 mg/kg BHA was around $10\;{\mu}M$. This in vivo concentration might offer some insights for the many in vitro cell culture studies on signal transduction and induction of phase II genes using similar concentrations. The oral bioavailability (F) of BHA was about 43% in the mice. In the mouse liver, BHA induced the expression of phase II genes including NQO-1, HO-1, ${\gamma}-GCS$, GST-pi and UGT 1A6, as well as some of the phase III transporter genes, such as MRP1 and Slco1b2. In addition, BHA activated distinct mitogen-activated protein kinases (MAPKs), c-Jun N-terminal kinase (JNK), extracellular signal-regulated protein kinase (ERK), as well as p38, suggesting that the MAPK pathways may play an important role in early signaling events leading to the regulation of gene expression including phase II drug metabolizing and some phase III drug transporter genes. This is the first study to demonstrate the in vivo pharmacokinetics of BHA, the in vivo activation of MAPK signaling proteins, as well as the in vivo induction of Phase II/III drug metabolizing enzymes/transporters in the mouse livers.

Effects of Lycii fructus extract on Experimentally Induced Liver Damage and Alloxan Diabetes in Rabbits (구기자(枸杞子) 추출물(抽出物)이 가토(家兎)의 실험적(實驗的) 간장장애(肝臟障碍) 및 alloxan당뇨병(糖尿病)에 미치는 영향(影響))

  • Sheo, Hwa-Joong;Jun, Sung-Joo;Lee, Myung-Yul
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.15 no.2
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    • pp.136-143
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    • 1986
  • These studies were carried out to investigate effects of Lycii fructus extract on experimentally CC14-induced liver damage and alloxan-induced diabetes in rabbits and acute toxicity using mice. $LD_{50}(mg/kg)$ of Lycii fructus extract(L.F.E.) was 12.17g/kg by intraperitoneal administration in mice. L.F.E. showed more rapid recuperation compared to the control group in CC14-intoxicated rabbits and 800mg/kg was the most effective. Especially GPT activity and total bilirubin level showed an apparant decreasing effect within 6 days and 8 days, respectively in 800mg/kg. But any differences were not observed in alkaline phosphatase and total cholesterol between sample and control group. Large amount administered group exhibited more excellent hypoglycemic effect in alloxan-induced diabetes of rabbits, that is, it was significant to the control group after 4 days and adjacent to the normal level on 12th day. And GPT activity was gradually decreased and showed clear decreasing effect after 6 days. It is suggested that L.F.E. can be administered not only as therapeutic agents (such as liver tonics or antidiabetetics) but also a natural food to shorten the recovery time of hepatic function in liver diseases and decrease the abnormally elevated blood glucose such as Diabetes Mellitus.

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Anti-inflammatory Effect of Onion (Allium cepa) Peel Hot Water Extract in vitro and in vivo (양파껍질 열수추출물의 in vitro 및 in vivo 항염증 효과)

  • Kang, Bo-Kyeong;Kim, Koth-Bong-Woo-Ri;Ahn, Na-Kyung;Choi, Yeon-Uk;Kim, Min-ji;Bark, Si-Woo;Pak, Won-Min;Kim, Bo-Ram;Park, Ji-Hye;Bae, Nan-Young;Ahn, Dong-Hyun
    • KSBB Journal
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    • v.30 no.4
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    • pp.148-154
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    • 2015
  • Onion (Allium cepa) is one of the flavonoids-rich materials in human diet and onion peel, which is the onion by-products, contains over 20 times more quercetin than the flesh. In this study, to examine the anti-inflammatory effects of onion peel hot water extract (OPHWE), the cell viability, nitric oxide (NO), pro-inflammatory cytokines, such as interluekin-6 (IL-6), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), and IL-$1{\beta}$, were measured using the murine macrophage cell line RAW 264.7 cells. The Balb/c mice were used for an in vivo acute toxicity test and ICR mice were used for measurement of inhibition effects of croton oil-induced mouse ear edema. As a result, NO levels decreased in a dose-dependent manner. The production of IL-6, TNF-${\alpha}$, and IL-$1{\beta}$ was suppressed by 38%, 41%, and 34% respectively, compared with that of the LPS only group, without any cytotoxicity. The edema formation in the ICR mouse ear was also reduced compared to that in control. Moreover, there were no mortalities occurred in mice administered 5,000 mg/kg body weight of OPHWE. These results suggest that OPHWE has considerable anti-inflammatory activities and can be regarded as a potent candidate material to treat inflammatory diseases.

Analysis on the Components and Safety Evaluation of Abeliophyllum distichum Nakai Leaves and Stems (미선나무 잎과 줄기의 성분 분석 및 안전성 평가)

  • Kwon, Soonbok;Kang, Heejoo;Kim, Minjung;Kim, Jinhee;Shin, Haeshik;Kim, Kangsung
    • Journal of Environmental Health Sciences
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    • v.40 no.3
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    • pp.234-244
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    • 2014
  • Objectives: This study was carried out in order to analyze the composition of the leaves and stems of Abeliophyllum distichum Nakai, with the aim of obtaining basic data for utilizing the plant as a food ingredient, as well as for processing. Methods: Leaves and stems from Abeliophyllum distichum Nakai were harvested at Cheongcheon-myeon, Geosan-gun, Chungcheongbuk-do, and were subsequently freeze-dried and ground to a fine powder for chemical component analysis and safety evaluation. Results: The moisture contents of Abeliophyllum distichum Nakai leaves and stems were respectively 65.07% and 40.97%, and the crude ash contents were 1.32% and 0.91%. In addition, the crude protein contents were 11.97% and 3.77%, and the crude fat contents were 2.52% and 0.36%, respectively. The fructose and glucose contents were 32.13 mg/g and 56.17 mg/g for leaves, and 11.38 mg/g and 10.59 mg/g for stems. The major fatty acids of the leaves were palmitic acid (31.79%) and stearic acid (14.79%), and those for stems were linolenic acid (32.78%) and palmitic acid (26.75%). The ascorbic acid contents of leaves and stems were 1.32 mg/g and 0.30 mg/g respectively. The calcium content was found to be the highest among the minerals tested, both in the leaves and stems, with the levels being 166.17 mg/100 g for leaves and 592.34 mg/100 g for stems. The content of organic acid was greater in leaves than in stems, with that of malic acid accounting for more than 75% of total organic acids for both samples. The total phenolic compounds and flavonoid contents of Abeliophyllum distichum Nakai were 50.64 mg/g and 13.53 mg/g in leaves and 96.47 mg/g and 18.53 mg/g in stems, respectively. No changes were shown in the number of micronucleated polychromatic erythrocytes (MNPCE) among 2,000 polychromatic erythrocytes compared to the negative control. Abeliophyllum distichum Nakai was administered orally to rats in order to investigate acute toxicity. The $LD_{50}$ values in rats were above 2,000 mg/kg. Conclusion: These results indicate that the leaves and stems of Abeliophyllum distichum Nakai can be used as natural ingredients in the development of nutritional and functional materials.

Is it Adequate to Determine Acetaminophen Toxicity Solely on Patients' History? An Analysis on Clinical Manifestation of Intoxication Patients with Positive Serum Acetaminophen Concentrations (환자의 아세트아미노펜 중독 여부를 환자진술 만으로 확인하는 것이 타당한가?: 혈중에서 아세트아미노펜이 검출된 환자의 임상 양상 분석)

  • Kim, Jee Hyun;Jeong, Won-joon;Ryu, Seung;Cho, Yong Chul;Moon, Jang Hyuck;Choi, Hyun Soo;Yang, Song Hee;Chung, Hee Sun
    • Journal of The Korean Society of Clinical Toxicology
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    • v.15 no.2
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    • pp.94-100
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    • 2017
  • Purpose: Acute acetaminophen intoxication is a common occurrence that can cause lethal complications. In most domestic emergency departments, clinicians tend to treat acetaminophen intoxication based on patients' history alone, simply due to the lack of a rapid acetaminophen laboratory test. We performed a 20-month study of intoxication patients to determine the correlation between the history of patients and serum laboratory tests for acetaminophen. Methods: We took blood samples from 280 intoxication patients to evaluate whether laboratory findings detected traces of acetaminophen in the sample. Patients were then treated according to their history. Laboratory results came out after patients' discharge. Agreement between patients' history and laboratory results were analyzed. Results: Among the 280 intoxicated patients enrolled, 38 patients had positive serum acetaminophen concentrations; 18 out of 38 patients did not represent a history suggesting acetaminophen intoxication. One patient without the history showed toxic serum acetaminophen concentration. Among the patients with the history, two patients with toxic serum acetaminophen concentration did not receive N-acetylcysteine (NAC) treatment due to their low reported doses, while other 2 patients without significant serum acetaminophen concentration did receive NAC treatment due to their high reported doses. Conclusion: This study showed a good overall agreement between history and laboratory test results. However, some cases showed inconsistencies between their history and laboratory test results. Therefore, in treating intoxication patients, a laboratory test of acetaminophen with rapid results should be available in most domestic emergency departments.